Deep Brain Stimulation (DBS) for Chronic Neuropathic Pain

The purpose of this study is to test the efficacy of DBS in a small cohort of patients with
chronic pain refractory to conventional treatments. The study will involve the implantation
of a neurostimulator, the Medtronic Activa PC+S device, to examine the efficacy of two modes
of DBS. Open-loop DBS will provide stimulation based on a pre-set schedule, whereas
closed-loop DBS will deliver stimulation based on brain activity associated with pain states.
The goals of this study are to identify neurophysiological correlates of elevated pain states
and find DBS parameters that disrupt pain-related brain activity and provide pain relief with
little or no side effects. The efficacy of pain relief on subtypes of pain syndromes will
also be studied.

Inclusion Criteria:

- Age ≥ 21 years

- Clinical diagnosis of post-stroke pain (thalamic pain), spinal cord injury or phantom
limb pain with allodynia or dysesthesia with pinprick anesthesia or hypoesthesia on
the affected hemibody or limb (anesthesia dolorosa).

- For Post-Stroke Pain: Stroke of ischemic etiology only. MRI done within one year of
the first visit showing a lesion that involves the contralateral brainstem, thalamus
or cortex. The lesion will involve cortical-subcortical areas in topography consistent
with sensory thalamocortical connections. This will include patients with infarcts in
the territory of the middle cerebral artery or those with cavernous malformations. A
more recent MRI may be required if the patient's condition changed within the previous
year.

- For Phantom limb pain: MRI done within one year not showing any contraindication to
surgery such as mass, lesion, hemorrhage or other abnormality near target

- For Spinal Cord Injury pain: MRI done within one year not showing contraindication to
surgery such as mass, lesion, hemorrhage or other abnormality near target

- One year or more of medically refractory severe pain (see below)

- Average daily pain for the past 30 days reported as >5 on a 0-10 numeric rating scale
(NRS)

- Failure to respond adequately to at least one antidepressant, one anti-seizure
medication and one oral narcotic with current stable doses of medications.

- Ability to speak / read English

- Capable of understanding and providing informed consent

- Stable doses of pain medications (e.g. anticonvulsant drug, anti-depressants, and
opioids etc.)

- Women of childbearing age must be on regular use of an accepted contraceptive
method(s).

Exclusion Criteria:

- Pregnancy or breast feeding

- Inability to speak and / or read English

- Inability to give informed consent

- Significant cognitive impairment or Dementia (MoCA < 25)

- Aphasia severe enough to limit the consent process or communication between the
investigators and the patient. Patients with mild or recovering aphasia may be
considered candidates at the discretion of the PI.

- Active depression (BDI > 20) or other untreated or uncontrolled psychiatric illness
(active general anxiety disorder, schizophrenia, bipolar disorder,
obsessive-compulsive disorder (OCD), or personality disorders (e.g. multiple
personality disorder, borderline personality disorder, etc.) or other neuropsychiatric
conditions that evaluating psychiatrist would recommend exclusion of patient after
neuropsychiatric evaluation.

- Suicide attempt
- History of substance abuse in past 3 years.

- Major medical co-morbidities increasing the risk of surgery including uncontrolled
hypertension, severe diabetes, major organ system failure, history of hemorrhagic
stroke, need for chronic anticoagulation other than aspirin, active infection,
immunocompromised state or malignancy with < 5 years life expectancy

- Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after
surgery. Patients taking these medications will need to discuss the need/risk of
continuing these medications with their physicians and the PI or study personnel may
contact the treating physician(s) as well to discuss the risks of anticoagulation /
antiaggregation therapy discontinuation.

- Coagulopathy. Patients will be excluded unless assessed and cleared by hematology.

- MRI (done within one year of the first visit) with significant abnormalities other
than those associated with the neurological disorder causing chronic pain.

- Implantable hardware not compatible with MRI or with the study.

- Inability to comply with study follow-up visits

- Previous ablative intracranial surgery for the management of the thalamic pain
syndrome.

- Previously implanted with deep brain stimulation system or any previously implanted
device treatment involving brain stimulation

- Major neurological disorder other than the one that led to the chronic pain including
epilepsy, neurodegenerative condition or any history of seizure

- Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic
stimulation (TMS) to treat a chronic condition

- Has an implanted electronic device such as a neurostimulator, cardiac pacemaker or
medication pump

- Allergies or known hypersensitivity to materials in the Activa PC+S system (i.e.
titanium, polyurethane, silicone, polyetherimide, stainless steel).

- Pregnancy or lack of regular use of contraceptives. Patients who become pregnant after
enrollment may be excluded from the study. Patients who become pregnant prior to the
surgical implantation of the DBS systems will be excluded from the study.

- Patients may be excluded from enrollment due to a condition that, in the judgment of
the PI, significantly increases risk or reduces significantly the likelihood of
benefit from DBS.